About the Project
Schizophrenia is a highly debilitating neurodevelopmental disorder impacting about 1% of the global population. While it is well established that schizophrenia is associated with altered function in key brain areas, such as the hippocampus, the precise cellular mechanisms are unknown. Recent studies highlight glutamatergic NMDA receptors (NMDA-Rs) as a key genetic risk factor for schizophrenia, consistent with convergent evidence for altered glutamate signalling in the brain of people with…
schizophrenia. Although NMDA-R dysfunction has been studied extensively at excitatory neurons, the impact of altered GABAergic interneuron function is poorly understood. This is important because emerging evidence implicates interneurons in schizophrenia. There are many subtypes of GABAergic cells. However, little research has looked at the diversity of interneuron subtypes. Our hypothesis is that Somatostatin interneurons will play a key role in the disorder, given NMDA-Rs are key to their normal function and they are known regulators of learning and neural plasticity in the developing and adult brain. The goal of this proposal is to explore how altered NMDA-R function impacts the properties of Somatostatin interneuron subtypes in the hippocampus, and in so doing better link the Glutamate and GABAergic hypotheses of Schizophrenia.
The project comprises three aims:
Aim 1: How do NMDA-R mutations impact the cellular properties of Somatostatin interneuron subtypes? The student will use electrophysiology, 2-photon uncaging and calcium imaging to explore how loss of NMDA-Rs impacts the intrinsic, synaptic and dendritic integration properties of Somatostatin interneurons. These findings will inform how mutations impact their respond to high-frequency inputs known to elicit plasticity in the brain.
Aim 2: To understand the molecular mechanisms underlying observed changes, we will perform bulk transcriptome analysis of fluorescently labelled Somatostatin interneuron subtypes in the hippocampus. Our hypothesis is that NMDA-R mutations will alter the expression of key synaptic proteins and dendritic ion channels. The student will use pharmacology to study the functional impact of gene expression changes, yielding possible targets to restore normal function.
Aim 3: How does altered interneuron function impact plasticity in the brain? The student will study how NMDA-R mutations impact hippocampal plasticity and the role of altered Somatostatin interneuron function in this process. Using targeted pharmacological and chemogenetic manipulations building on results from aims 1 and 2, they will determine if it is possible to restore normal plasticity by modulating the activity of different Somatostatin populations. This interdisciplinary project will combine expertise in cellular physiology and neural circuits at the University of Bristol and genomic research into neurodevelopmental disorders at the University of Exeter. The proposal builds on shared interest in the neurobiology of schizophrenia across all labs and recent work exploring the diversity, neuromodulation, and role in plasticity of different interneuron subtypes.
The proposal will provide training in a cutting-edge array of experimental methods, including transgenic models of mental health disorders, electrophysiology, 2-photon imaging, pharmacology, genetic analysis of neural cell types and viral tools to label and manipulate neurons. The student will be led by the supervisory team but encouraged to take ownership of the project over the course of the PhD.
The student will be able to increase, or decrease the relative focus of different sub-aims based on their specific interests or experimental outcomes. For example, expanding more on the specific circuit-level deficits that emerge downstream of synaptic changes using optogenetic circuit mapping, focusing on the molecular mechanisms or ion channels pulled out from the genetic screen, or exploring different plasticity paradigms and the molecular/cellular influences on learning and memory. The supervisory team have extensive experience across these different domains and all the necessary equipment to expand the project in different directions are in place.
In summary, the project will develop novel understanding into the altered function of key cell types in models of neurodevelopmental disorders. This project will integrate more widely into research being undertaken across the GW4 as part of a wider MRC funded MURIDAE project to understand how NMDA-R mutations alter the formation and function of key brain circuits and associated behaviours. The pharmacological studies will provide insight to ground future therapeutic approaches to develop new drugs for the treatment of schizophrenia and the underlying mechanisms through which they work.
How to Apply
A list of all the projects and how to apply is available on the GW4 BioMed website at gw4biomed.ac.uk. You may select up to 2 projects and submit one application per candidate only.
Please complete an application to the GW4 BioMed3 for an ‘offer of funding’. If successful, you will also need to make an application for an 'offer to study' to your chosen institution later.
Please complete the online application form linked from our website by 5.00pm on Wednesday, 21st October 2026. Please note that we may close the application process before the stated deadline if an unprecedented number of applications are received– check the GW4 BioMed website for details and updates. If you are shortlisted for interview, you will be notified from Tuesday, 22nd December 2026. Interviews will be held virtually on 26th and 27th January 2027. Studentships will start on 1st October 2027.
Further Information
For informal enquiries, please contact
GW4BioMed@cardiff.ac.uk
For project related queries, please contact the respective supervisors listed on the project descriptions on the GW4 BioMed website.
Funding Notes
These studentships are funded through GW4 BioMed3 MRC Doctoral Landscape Programme and consist of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£21, 805 p.a. for 2026/27, updated each year).
Additional research training and support funding of up to £5,000 per annum is also available.
References
Anastasiades PG*, Collins DP*, Carter AG (2021). Mediodorsal and ventromedial thalamus engage distinct L1 circuits in the prefrontal cortex. Neuron. Jan 20;109(2):314-330
Anastasiades PG, et al., (2019). Cell-type-specific D1 dopamine receptor modulation of projection neurons and interneurons in the prefrontal cortex. Cerebral Cortex. Jul 5;29(7):3224-3242
Udakis, M., et al. (2025) Hippocampal OLM interneurons regulate CA1 place cell plasticity and remapping. Nat Commun 16, 9912.
Udakis, M., et al. (2020) Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output. Nat Commun 11, 4395.
Griesius, S., et al. (2022) Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity. Neuropsychopharmacol. 47, 1367–1378.
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